Systemic lupus erythematosus (SLE) is a disease known for its multiple manifestations, including numerous cardiac complications. While pericardial effusions are common in patients with SLE, cardiac tamponade is rare, and it is even rarer as an initial and isolated clinical manifestation of SLE. We describe a case of a young adult woman who presented with a four-week history of shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea. Chest radiography revealed a significant increase in the cardiothoracic index, and transthoracic echocardiography confirmed a life-threatening cardiac tamponade that necessitated emergency pericardiocentesis and high-dose corticosteroids. Following a thorough investigation, we excluded viral infection, malignancy, tuberculosis, and other autoimmune diseases, and the patient was diagnosed with SLE based on the Systemic Lupus International Collaborating Clinics (SLICC) criteria. In this case report, we also present an uncommon association between SLE and primary biliary cholangitis (PBC). While both are autoimmune diseases, the coexistence of these two conditions in the same patient is rare. The report highlights the need for ongoing research to better understand the optimal management strategies for patients with coexisting autoimmune conditions.